Lack of cyclin D2 impairing adult brain neurogenesis alters hippocampal-dependent behavioral tasks without reducing learning ability

Abstract

The exact function of the adult brain neurogenesis remains elusive, although it has been suggested to play a role in learning and memory processes. In our studies, we employed cyclin D2 gene knockout (cD2 KO) mice showing impaired neurogenesis as well as decreased hippocampal size. However, irrespectively of the genetic background of cD2 KO mice, this phenotype resulted in neither deficits in the hippocampal-dependent learning ability nor the memory formation. In the present study, cD2 KO mice and control littermates were subjected to hippocampal-dependent behavioral tests with little or no learning component. The knockout mice showed significant impairment in such species-typical behaviors as nest construction, digging, and marble burying. They were building none or poorer nests, digging less robustly, and burying fewer marbles than control mice. Such impairments were previously described, e.g., in animals with hippocampal lesions. Moreover, cD2 KO animals were also more active in the open field and automated motility chamber as well as showed increased explorative behavior in IntelliCage. Both increased motility and explorative behaviors were previously observed in hippocampally lesioned animals. Finally, cD2 KO mice showed normal sucrose preference, however starting from the second exposure to the sweetened solution, while control animals displayed a strong preference immediately. Presented results suggest that either morphological abnormalities of the hippocampal formation or adult brain neurogenesis impairment (or both) alter hippocampal-dependent behaviors of mutant mice without influencing learning abilities. These results may also suggest that adult brain neurogenesis is involved in species-typical behaviors.

Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine

“…On the contrary, the immobility was reduced in these mice. We have observed before cD2 KO animals to be more active and explorative (Jedynak et al, 2012;Ben Abdallah et al, 2013). Please note, we were still able to increase immobility in mutant mice by UCMS and again reduce it through chronic fluoxetine treatment.…”

“…There is also possibility of compensatory mechanisms to operate in these mice (discussed in Jaholkowski et al, 2009), however, the model is recognized as valuable and adequate tool in the field (for review see Frankland, 2013). The results obtained with the use of cD2 KO mice suggested the lack of relevance of adult brain neurogenesis for learning and memory in general (Jaholkowski et al, 2009) e a view which is now widely accepted (e.g., Sahay et al, 2011) e while suggested and/or confirmed the role of this process in particular aspects of learning (Ben Abdallah et al, 2013), smell detection (Jaholkowski et al, 2009), species-typical behaviors (Jedynak et al, 2012), and alcohol consumption (Jaholkowski et al, 2011). Most of transgenic models with manipulated adult hippocampal neurogenesis, in contrast to our model, do not achieve complete ablation of newborn neurons.…”

“…The test was performed 24 h after the termination of UCMS and fluoxetine treatment, it was done as described previously (Jedynak et al, 2012). The apparatus was a wooden floor (50 cm  50 cm) surrounded by 34 cm high walls.…”

“…We showed before that mice with mutated cyclin D2 gene display largely impaired proliferation of neuronal precursors in SGZ (Kowalczyk et al, 2004;Jaholkowski et al, 2009;Jedynak et al, 2012). Notably, cyclin D2 mutant mice show deficits in some hippocampal-dependent behaviors (Jedynak et al, 2012), but not in learning in general (Jaholkowski et al, 2009;Jedynak et al, 2012;Urbach et al, 2013), while selected cognitive functions are impaired (Ben Abdallah et al, 2013;Garthe et al, 2014).…”

How to keep proliferative neural stem/progenitor cells

“…27 In cyclin D2-knockout mice, the brain size is smaller and adult neurogenesis is dramatically impaired. [28][29][30][31] Cyclin D2 is essential for expansion of the NSPCs in both embryonic and adult brains, but what is the significance of the biased localization of cyclin D2 in the basal endfoot of the APs? Figure 1.…”